Muscle Adaptations to Heavy-Load and Blood Flow Restriction Resistance Training Methods.

Resistance-based blood flow restriction training (BFRT) improves skeletal muscle strength and size. Unlike heavy-load resistance training (HLRT), there is debate as to whether strength adaptations following BFRT interventions can be primarily attributed to concurrent muscle hypertrophy, as the magnitude of hypertrophy is often minor. The present study aimed to investigate the effect of 7 weeks of BFRT and HLRT on muscle strength and hypertrophy. The expression of protein growth markers from muscle biopsy samples was also measured. Male participants were allocated to moderately heavy-load training (HL; n = 9), low-load BFRT (LL + BFR; n = 8), or a control (CON; n = 9) group to control for the effect of time. HL and LL + BFR completed 21 training sessions (3 d.week-1) comprising bilateral knee extension and knee flexion exercises (HL = 70% one-repetition maximum (1-RM), LL + BFR = 20% 1-RM + blood flow restriction). Bilateral knee extension and flexion 1-RM strength were assessed, and leg muscle CSA was measured via peripheral quantitative computed tomography. Protein growth markers were measured in vastus lateralis biopsy samples taken pre- and post the first and last training sessions. Biopsy samples were also taken from CON at the same time intervals as HL and LL + BFR. Knee extension 1-RM strength increased in HL (19%) and LL + BFR (19%) but not CON (2%; p < 0.05). Knee flexion 1-RM strength increased similarly between all groups, as did muscle CSA (50% femur length; HL = 2.2%, LL + BFR = 3.0%, CON = 2.1%; TIME main effects). 4E-BP1 (Thr37/46) phosphorylation was lower in HL and LL + BFR immediately post-exercise compared with CON in both sessions (p < 0.05). Expression of other growth markers was similar between groups (p > 0.05). Overall, BFRT and HLRT improved muscle strength and size similarly, with comparable changes in intramuscular protein growth marker expression, both acutely and chronically, suggesting the activation of similar anabolic pathways. However, the low magnitude of muscle hypertrophy was not significantly different to the non-training control suggesting that strength adaptation following 7 weeks of BFRT is not driven by hypertrophy, but rather neurological adaptation.

High intensity interval training versus moderate intensity continuous training for people with interstitial lung disease: protocol for a randomised controlled trial.

BACKGROUND: Interstitial lung disease is a debilitating condition associated with significant dyspnoea, fatigue, and poor exercise tolerance. Pulmonary rehabilitation is an effective and key intervention in people with interstitial lung disease. However, despite the best efforts of patients and clinicians, many of those who participate are not achieving clinically meaningful benefits. This assessor-blinded, multi-centre, randomised controlled trial aims to compare the clinical benefits of high intensity interval exercise training versus the standard pulmonary rehabilitation method of continuous training at moderate intensity in people with fibrotic interstitial lung disease. METHODS: Eligible participants will be randomised to either a standard pulmonary rehabilitation group using moderate intensity continuous exercise training or high intensity interval exercise training. Participants in both groups will undertake an 8-week pulmonary rehabilitation program of twice-weekly supervised exercise training including aerobic (cycling) and strengthening exercises. In addition, participants in both groups will be prescribed a home exercise program. Outcomes will be assessed at baseline, upon completion of the intervention and at six months following the intervention by a blinded assessor. The primary outcome is endurance time on a constant work rate test. Secondary outcomes are functional capacity (6-min walk distance), health-related quality of life (Chronic Respiratory Disease Questionnaire (CRQ), St George's Respiratory Questionnaire idiopathic pulmonary fibrosis specific version (SGRQ-I), breathlessness (Dyspnoea 12, Modified Medical Research Council Dyspnoea Scale), fatigue (fatigue severity scale), anxiety (Hospital Anxiety and Depression Scale), physical activity level (GeneActiv), skeletal muscle changes (ultrasonography) and completion and adherence to pulmonary rehabilitation. DISCUSSION: The standard exercise training strategies used in pulmonary rehabilitation may not provide an optimal exercise training stimulus for people with interstitial lung disease. This study will determine whether high intensity interval training can produce equivalent or even superior changes in exercise performance and symptoms. If high intensity interval training proves effective, it will provide an exercise training strategy that can readily be implemented into clinical practice for people with interstitial lung disease. Trial registration ClinicalTrials.gov Registry (NCT03800914). Registered 11 January 2019, https://clinicaltrials.gov/ct2/show/NCT03800914 Australian New Zealand Clinical Trials Registry ACTRN12619000019101. Registered 9 January 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376050&isReview=true.

Home-based or remote exercise testing in chronic respiratory disease, during the COVID-19 pandemic and beyond: A rapid review.

OBJECTIVES: To identify exercise tests that are suitable for home-based or remote administration in people with chronic lung disease. METHODS: Rapid review of studies that reported home-based or remote administration of an exercise test in people with chronic lung disease, and studies reporting their clinimetric (measurement) properties. RESULTS: 84 studies were included. Tests used at home were the 6-minute walk test (6MWT, two studies), sit-to-stand tests (STS, five studies), Timed Up and Go (TUG, 4 studies) and step tests (two studies). Exercise tests administered remotely were the 6MWT (two studies) and step test (one study). Compared to centre-based testing the 6MWT distance was similar when performed outdoors but shorter when performed at home (two studies). The STS, TUG and step tests were feasible, reliable (intra-class correlation coefficients >0.80), valid (concurrent and known groups validity) and moderately responsive to pulmonary rehabilitation (medium effect sizes). These tests elicited less desaturation than the 6MWT, and validated methods to prescribe exercise were not reported. DISCUSSION: The STS, step and TUG tests can be performed at home, but do not accurately document desaturation with walking or allow exercise prescription. Patients at risk of desaturation should be prioritised for centre-based exercise testing when this is available.

Overexpression of NDRG2 in skeletal muscle does not ameliorate the effects of stress in vivo.

NEW FINDINGS: What is the central question of this study? Do elevated levels of the stress-response protein NDRG2 protect against fasting and chronic disease in mouse skeletal muscle? What is the main finding and its importance? NDRG2 levels increased in the tibialis anterior muscle in response to fasting and the effects of motor neurone disease. No alleviation of the stress-related and proteasomal pathways, mitochondrial dysfunction or muscle mass loss was observed even with the addition of exogenous NDRG2 indicating that the increase in NDRG2 is a normal adaptive response. ABSTRACT: Skeletal muscle mass loss and dysfunction can arise from stress, which leads to enhanced protein degradation and metabolic impairment. The expression of N-myc downstream-regulated gene 2 (NDRG2) is induced in response to different stressors and is protective against the effects of stress in some tissues and cell types. Here, we investigated the endogenous NDRG2 response to the stress of fasting and chronic disease in mice and whether exogenous NDRG2 overexpression through adeno-associated viral (AAV) treatment ameliorated the response of skeletal muscle to these conditions. Endogenous levels of NDRG2 increased in the tibialis anterior muscle in response to 24 h fasting and with the development of the motor neurone disease, amyotrophic lateral sclerosis, in SOD1G93A transgenic mice. Despite AAV-induced overexpression and increased expression with fasting, NDRG2 was unable to protect against the activation of proteasomal and stress pathways in response to fasting. Furthermore, NDRG2 was unable to reduce muscle mass loss, mitochondrial dysfunction and elevated oxidative and endoplasmic reticulum stress levels in SOD1G93A mice. Conversely, elevated NDRG2 levels did not exacerbate these stress responses. Overall, increasing NDRG2 levels might not be a useful therapeutic strategy to alleviate stress-related disease pathologies in skeletal muscle.

Is there rationale for the cuff pressures prescribed for blood flow restriction exercise? A systematic review.

BACKGROUND: Blood flow restriction exercise has increasingly broad applications among healthy and clinical populations. Ensuring the technique is applied in a safe, controlled, and beneficial way for target populations is essential. Individualized cuff pressures are a favored method for achieving this. However, there remains marked inconsistency in how individualized cuff pressures are applied. OBJECTIVES: To quantify the cuff pressures used in the broader blood flow restriction exercise literature, and determine whether there is clear justification for the choice of pressure prescribed. METHODS: Studies were included in this review from database searches if they employed an experimental design using original data, involved either acute or chronic exercise using blood flow restriction, and they assessed limb or arterial occlusion pressure to determine an individualized cuff pressure. Methodologies of the studies were evaluated using a bespoke quality assessment tool. RESULTS: Fifty-one studies met the inclusion criteria. Individualized cuff pressures ranged from 30% to 100% arterial occlusion pressure. Only 7 out of 52 studies attempted to justify the individualized cuff pressure applied during exercise. The mean quality rating for all studies was 11.1 ± 1.2 out of 13. CONCLUSIONS: The broader blood flow restriction exercise literature uses markedly heterogeneous prescription variables despite using individualized cuff pressures. This is problematic in the absence of any clear justification for the individualized cuff pressures selected. Systematically measuring and reporting all relevant acute responses and training adaptations to the full spectrum of BFR pressures alongside increased clarity around the methodology used during blood flow restriction exercise is paramount.

The Effects of Early-Onset Pre-Eclampsia on Placental Creatine Metabolism in the Third Trimester.

Creatine is a metabolite important for cellular energy homeostasis as it provides spatio-temporal adenosine triphosphate (ATP) buffering for cells with fluctuating energy demands. Here, we examined whether placental creatine metabolism was altered in cases of early-onset pre-eclampsia (PE), a condition known to cause placental metabolic dysfunction. We studied third trimester human placentae collected between 27-40 weeks' gestation from women with early-onset PE (n = 20) and gestation-matched normotensive control pregnancies (n = 20). Placental total creatine and creatine precursor guanidinoacetate (GAA) content were measured. mRNA expression of the creatine synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT), the creatine transporter (SLC6A8), and the creatine kinases (mitochondrial CKMT1A & cytosolic BBCK) was assessed. Placental protein levels of arginine:glycine aminotransferase (AGAT), GAMT, CKMT1A and BBCK were also determined. Key findings; total creatine content of PE placentae was 38% higher than controls (p < 0.01). mRNA expression of GATM (p < 0.001), GAMT (p < 0.001), SLC6A8 (p = 0.021) and BBCK (p < 0.001) was also elevated in PE placentae. No differences in GAA content, nor protein levels of AGAT, GAMT, BBCK or CKMT1A were observed between cohorts. Advancing gestation and birth weight were associated with a down-regulation in placental GATM mRNA expression, and a reduction in GAA content, in control placentae. These relationships were absent in PE cases. Our results suggest PE placentae may have an ongoing reliance on the creatine kinase circuit for maintenance of cellular energetics with increased total creatine content and transcriptional changes to creatine synthesizing enzymes and the creatine transporter. Understanding the functional consequences of these changes warrants further investigation.

Chronic Blood Flow Restriction Exercise Improves Objective Physical Function: A Systematic Review.

Background: Blood flow restriction or KAATSU exercise training is associated with greater muscle mass and strength increases than non-blood flow restriction equivalent exercise. Blood flow restriction exercise has been proposed as a possible alternative to more physically demanding exercise prescriptions (such as high-load/high-intensity resistance training) in a range of clinical and chronic disease populations. While the maintenance of muscle mass and size with reduced musculoskeletal tissue loading appeals in many of these physically impaired populations, there remains a disconnect between some of the desired clinical measures for chronic disease populations and those commonly measured in the literature examining blood flow restriction exercise. While strength does play a vital role in physical function, task-specific objective measures of physical function indicative of activities of daily living are often more clinically relevant and applicable for evaluating the success of medical and surgical interventions or monitoring age- and disease-related physical decline. Objective: To determine whether exercise interventions utilizing blood flow restriction are able to improve objective measures of physical function indicative of activities of daily living. Methods: A systematic search of Medline, Embase, CINAHL, SPORTDiscus, and Springer identified 13 randomized control trials utilizing an exercise intervention combined with blood flow restriction, while measuring at least one objective measure of physical function. Participants were ≥18 years of age. Systematic review of the literature and quality assessment of the included studies used the Cochrane Collaboration's tool for assessing risk bias. Results: Data from 13 studies with a total of 332 participants showed blood flow restriction exercise, regardless of modality, most notably increased performance on the 30 s sit-to-stand and timed up and go tests, and generally improved physical function on other tests including walking tests, variations of sit-to-stand tests, and balance, jumping, and stepping tests. Conclusions: From the evidence available, blood flow restriction exercise of multiple modalities improved objective measures of physical function indicative of activities of daily living.

The Effects of Restriction Pressures on the Acute Responses to Blood Flow Restriction Exercise.

PURPOSE: No current guidelines or recommendations exist informing the selection of restriction pressure during blood flow restriction exercise (BFRE). Moreover, the effects of specific relative restriction pressures on the acute muscle, metabolic and cardiopulmonary responses to BFRE are unclear. The purpose of this study was to characterize these acute responses at different levels of restriction pressure. METHODS: Participants (n = 10) completed rhythmic isometric knee extension exercise across five experimental trials in a balanced randomized order. Three were BFRE trials {B-40 [restriction pressure set to 40% LOP (total limb occlusion pressure)]; B-60 (60% LOP); and B-80 (80% LOP)} with a workload equivalent to 20% maximal voluntary force (MVC), one was non-BFRE at 20% MVC (LL) and one was non-BFRE at 80% MVC (HL). Measurements recorded were torque, muscle activity via electromyography (EMG), tissue oxygenation via near infrared spectroscopy, whole body oxygen consumption, blood lactate and heart rate. RESULTS: For the LL and B-40 trials, most measures remained constant. However, for the B-60 and B-80 trials, significant fatigue was demonstrated by a reduction in MVC torque across the trial (p < 0.05). Blood lactate increased from baseline in HL, B-60, and B-80 (p < 0.05). Submaximal EMG was greater in B-60 and B-80 than LL, but lower compared with HL (p < 0.05). Tissue oxygenation decreased in HL, B-40, B-60, and B-80 (p < 0.05), which was lower in the B-80 trial compared to all other trials (p < 0.01). Whole body oxygen consumption was not different between the BFRE trials (p > 0.05). CONCLUSION: We demonstrate graded/progressive acute responses with increasing applied pressure during BFRE, from which we speculate that an effective minimum "threshold" around 60% LOP may be necessary for BFRE to be effective with training. While these data provide some insight on the possible mechanisms by which BFRE develops skeletal muscle size and strength when undertaken chronically across a training program, the outcomes of chronic training programs using different levels of applied restriction pressures remain to be tested. Overall, the present study recommends 60-80% LOP as a suitable "minimum" BFRE pressure.

Placental creatine metabolism in cases of placental insufficiency and reduced fetal growth.

Creatine is a metabolite involved in cellular energy homeostasis. In this study, we examined placental creatine content, and expression of the enzymes required for creatine synthesis, transport and the creatine kinase reaction, in pregnancies complicated by low birthweight. We studied first trimester chorionic villus biopsies (CVBs) of small for gestational age (SGA) and appropriately grown infants (AGA), along with third trimester placental samples from fetal growth restricted (FGR) and healthy gestation-matched controls. Placental creatine and creatine precursor (guanidinoacetate-GAA) levels were measured. Maternal and cord serum from control and FGR pregnancies were also analyzed for creatine concentration. mRNA expression of the creatine transporter (SLC6A8); synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT); mitochondrial (mtCK) and cytosolic (BBCK) creatine kinases; and amino acid transporters (SLC7A1 & SLC7A2) was assessed in both CVBs and placental samples. Protein levels of AGAT (arginine:glycine aminotransferase), GAMT, mtCK and BBCK were also measured in placental samples. Key findings; total creatine content of the third trimester FGR placentae was 43% higher than controls. The increased creatine content of placental tissue was not reflected in maternal or fetal serum from FGR pregnancies. Tissue concentrations of GAA were lower in the third trimester FGR placentae compared to controls, with lower GATM and GAMT mRNA expression also observed. No differences in the mRNA expression of GATM, GAMT or SLC6A8 were observed between CVBs from SGA and AGA pregnancies. These results suggest placental creatine metabolism in FGR pregnancies is altered in late gestation. The relevance of these changes on placental bioenergetics should be the focus of future investigations.

Lower body blood flow restriction training may induce remote muscle strength adaptations in an active unrestricted arm.

PURPOSE: We examined the concurrent characteristics of the remote development of strength and cross-sectional area (CSA) of upper body skeletal muscle in response to lower body resistance training performed with an applied blood flow restriction (BFR). METHODS: Males allocated to an experimental BFR group (EXP; n = 12) or a non-BFR control group (CON; n = 12) completed 7-weeks of resistance training comprising three sets of unilateral bicep curls [50% 1-repetition maximum (1-RM)], then four sets of bilateral knee extension and flexion exercises (30% 1-RM). EXP performed leg exercises with an applied BFR (60% limb occlusion pressure). 1-RM strength was measured using bilateral leg exercises and unilateral bicep curls in both trained and untrained arms. Muscle CSA was measured via peripheral quantitative computed tomography in the dominant leg and both arms. RESULTS: 1-RM in the trained arm increased more in EXP (2.5 ± 0.4 kg; mean ± SEM) than the contralateral untrained arm (0.8 ± 0.4 kg), and the trained arm of CON (0.6 ± 0.3 kg, P < 0.05). The increase in knee extension 1-RM was twofold that of CON (P < 0.01). Knee flexion 1-RM, leg CSA, and trained arm CSA increased similarly between groups (P > 0.05), while untrained arm CSA did not change (P > 0.05). CONCLUSION: Lower limb BFR training increased trained arm strength more than the contralateral untrained arm, and the trained arm of controls. However, there was no additional effect on muscle CSA. These findings support evidence for a BFR training-derived remote strength transfer that may be relevant to populations with localised movement disorders.

Hemodynamic responses are reduced with aerobic compared with resistance blood flow restriction exercise.

The hemodynamics of light-load exercise with an applied blood-flow restriction (BFR) have not been extensively compared between light-intensity, BFR, and high-intensity forms of both resistance and aerobic exercise in the same participant population. Therefore, the purpose of this study was to use a randomized crossover design to examine the hemodynamic responses to resistance and aerobic BFR exercise in comparison with a common high-intensity and light-intensity non-BFR exercise. On separate occasions participants completed a leg-press (resistance) or treadmill (aerobic) trial. Each trial comprised a light-intensity bout (LI) followed by a light-intensity bout with BFR (80% resting systolic blood pressure (LI+BFR)), then a high-intensity bout (HI). To characterize the hemodynamic response, measures of cardiac output, stroke volume, heart rate and blood pressure were taken at baseline and exercise for each bout. Exercising hemodynamics for leg-press LI+BFR most often resembled those for HI and were greater than LI (e.g. for systolic blood pressure LI+BFR = 152 ± 3 mmHg; HI = 153 ± 3; LI = 143 ± 3 P < 0.05). However, exercising hemodynamics for treadmill LI+BFR most often resembled those for LI and were lower than HI (e.g. for systolic pressure LI+BFR = 124 ± 2 mmHg; LI = 123 ± 2; HI = 140 ± 3 P < 0.05). In conclusion, the hemodynamic response for light aerobic (walking) BFR exercise suggests this mode of BFR exercise may be preferential for chronic use to develop muscle size and strength, and other health benefits in certain clinical populations that are contraindicated to heavy-load resistance exercise.

Haemodynamics of aerobic and resistance blood flow restriction exercise in young and older adults.

PURPOSE: Light-load blood flow restriction exercise (BFRE) may provide a novel training method to limit the effects of age-related muscle atrophy in older adults. Therefore, the purpose of this study was to compare the haemodynamic response to resistance and aerobic BFRE between young adults (YA; n = 11; 22 ± 1 years) and older adults (OA; n = 13; 69 ± 1 years). METHOD: On two occasions, participants completed BFRE or control exercise (CON). One occasion was leg press (LP; 20 % 1-RM) and the other was treadmill walking (TM; 4 km h(-1)). Haemodynamic responses (HR, Q, SV and BP) were recorded during baseline and exercise. RESULT: At baseline, YA and OA were different for some haemodynamic parameters (e.g. BP, SV). The relative responses to BFRE were similar between YA and OA. Blood pressures increased more with BFRE, and also for LP over TM. Q increased similarly for BFRE and CON (in both LP and TM), but with elevated HR and reduced SV (TM only). CONCLUSION: While BFR conferred slightly greater haemodynamic stress than CON, this was lower for walking than leg-press exercise. Given similar response magnitudes between YA and OA, these data support aerobic exercise being a more appropriate BFRE for prescription in older adults that may contribute to limiting the effects of age-related muscle atrophy.